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Updated: Jul 4, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Inhibition of protein kinase C beta II downregulates tristetraprolin expression in activated macrophages

T Leppänen1, U Jalonen, H Kankaanranta

  • 1The Immunopharmacology Research Group, Medical School, University of Tampere and Research Unit, Tampere University Hospital, Tampere, Finland.

Inflammation Research : Official Journal of the European Histamine Research Society ... [Et Al.]
|July 3, 2008
PubMed
Abstract

Insights

Classical protein kinase C (cPKC) upregulates tristetraprolin (TTP) expression in macrophages, potentially via transcription factor AP-2, offering a new insight into PKC beta's role in inflammation.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Tristetraprolin (TTP) is an anti-inflammatory protein that destabilizes cytokine mRNAs.
  • Understanding the regulation of TTP is crucial for controlling inflammatory responses.

Purpose of the Study:

  • To investigate the role of classical protein kinase C isoenzymes (cPKC) in regulating TTP expression in activated macrophages.

Main Methods:

  • J774 macrophages were stimulated with LPS and PMA to induce TTP expression.
  • Western blotting and quantitative RT-PCR were used to assess TTP protein and mRNA levels.
  • The effects of cPKC inhibitors and downregulation on TTP expression were analyzed, along with transcription factor activation.

Main Results:

  • Inhibitors of cPKC, including CGP53353, significantly reduced LPS and PMA-induced TTP expression.
  • Downregulation of cPKC also decreased TTP protein and mRNA levels.
  • CGP53353 treatment inhibited the activation of transcription factor AP-2.

Conclusions:

  • Classical protein kinase C (cPKC), particularly PKC beta II, upregulates TTP expression in activated macrophages.
  • This regulation appears to be mediated through the activation of transcription factor AP-2.
  • This finding reveals an additional mechanism by which PKC beta influences inflammatory processes.

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